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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04454788




Registration number
NCT04454788
Ethics application status
Date submitted
16/06/2020
Date registered
2/07/2020
Date last updated
22/09/2020

Titles & IDs
Public title
Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients With Large Vessel Occlusion
Scientific title
Extending the Time Window for Tenecteplase by Effective Reperfusion of peNumbrAL Tissue in Patients With Large Vessel Occlusion
Secondary ID [1] 0 0
2019.125
Universal Trial Number (UTN)
Trial acronym
ETERNAL-LVO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tenecteplase
Treatment: Drugs - Standard Care (which may include intravenous Alteplase)

Experimental: Intravenous tenecteplase (TNK) - Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).

Active Comparator: Intravenous tissue plasminogen activator (tPA) - Patients will receive standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.


Treatment: Drugs: Tenecteplase
Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as intravenous bolus over 5-10 seconds

Treatment: Drugs: Standard Care (which may include intravenous Alteplase)
Patients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS - Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2) at 90 days
Timepoint [1] 0 0
90 days
Secondary outcome [1] 0 0
Early clinical improvement - Reduction in National Institutes of Health Stroke Scale (NIHSS) score of =8 points at 24 hours or reaching NIHSS 0-1
Timepoint [1] 0 0
24 hours
Secondary outcome [2] 0 0
Modified Rankin Scale (mRS) 0-2 (functional independence) - Modified Rankin Scale (mRS) 0-2 (functional independence) at 90 days
Timepoint [2] 0 0
90 days
Secondary outcome [3] 0 0
Substantial reperfusion at initial angiographic assessment - Proportion of patients with >50% reperfusion of the affected vascular territory (mTICI 3b/3) on initial digital subtraction angiography prior to thrombectomy
Timepoint [3] 0 0
initial angiography within 24 hours of stroke onset
Secondary outcome [4] 0 0
Symptomatic intracerebral hemorrhage (sICH) - sICH defined as parenchymal hematoma type 2 (PH2) - blood clot occupying >30% of the infarcted territory with substantial mass effect
Timepoint [4] 0 0
24 hours post-randomization
Secondary outcome [5] 0 0
Death due to any cause
Timepoint [5] 0 0
90 days
Secondary outcome [6] 0 0
Modified Rankin Scale (mRS) 5-6 - Poor functional outcome of death or requirement for fulltime nursing care
Timepoint [6] 0 0
90 days
Secondary outcome [7] 0 0
Successful reperfusion at 24 hours - Reperfusion (defined as >90% and >50% reduction in perfusion lesion volume)
Timepoint [7] 0 0
24 hours
Secondary outcome [8] 0 0
Infarct growth - Increase in the volume of irreversibly injured brain between pre-treatment and 24 hour imaging
Timepoint [8] 0 0
24 hours
Secondary outcome [9] 0 0
Recanalization - Change in vessel patency between pre-treatment and 24h imaging (CT or MR angiography)
Timepoint [9] 0 0
24 hours

Eligibility
Key inclusion criteria
- Patients presenting with acute hemispheric ischemic stroke with onset (or the time
they last known to be well) within 24 hours.

- Patient's age is =18 years.

- Premorbid mRS <3, with a concurrent assessment of whether the patient was able,
immediately prior to the stroke, to: 1) Drive, or (if never drives) perform own
Domestic duties, and 2) Shop for themselves, and 3) Bank/do their own finances (i.e.
Drive/Domestic, Bank, Shop = DBS +ve). Need to be DBS +ve to be study eligible.

- Presence of a vessel occlusion on CTA or MRA. LVO will be defined as 'potentially
retrievable' thrombus at one or more of the following sites: intracranial internal
carotid (ICA), middle cerebral artery (MCA) first segment (M1), proximal middle
cerebral artery second segment (M2) or isolated/tandem occlusion of the extracranial
ICA. Patients with an extracranial ICA stenosis and occlusion are also eligible.

- Presence of 'target mismatch' on automated perfusion CT (CTP) or diffusion-perfusion
MRI software defined as an ischemic core of <100mL, penumbra of >20mL and an ischemic
core to perfusion lesion ratio of >1.8
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Intracranial hemorrhage (ICH) or other diagnosis (e.g. tumor).

- Basilar Artery occlusion.

- Extensive early ischemic change (hypodensity on NCCT or high signal on DWI-MRI) or
early ischemic change outside the perfusion lesion that invalidates mismatch criteria.

- Pre-stroke mRS score of > 2 (indicating significant previous disability) or DBS -ve.

- Any terminal illness such that patient would not be expected to survive more than 1
year

- Any condition that, in the judgment of the investigator could impose hazards to the
patient if study therapy is initiated or affect the participation of the patient in
the study.

- Pregnant women.

- Other standard contraindications to thrombolysis.

- Minor stroke symptoms, or major stroke symptoms rapidly improving

- Clinical presentation suggesting subarachnoid haemorrhage

- Known bleeding diasthesis and/or platelet count <100,000 or taking warfarin with INR >
1.7.

- Patients who have received heparin within 48 hours must have normal aPTT.

- Major surgery or serious trauma within 14 days, serious head trauma within 3 months.

- GI or urinary tract haemorrhage within last 21 days

- Arterial puncture at a non-compressible site or lumbar puncture within 7 days

- Systolic BP > 185, diastolic BP > 110mmHg

- Clinical stroke within 3 months or history of ICH

- Unable to gain consent from patient or person responsible

- Known severe renal impairment (GFR < 15mls/min)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [4] 0 0
Box Hill Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Liverpool
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment postcode(s) [3] 0 0
3050 - Melbourne
Recruitment postcode(s) [4] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Patients presenting to the emergency department with an acute ischemic stroke due to a large
vessel occlusion eligible for thrombectomy and target mismatch on computed tomography
perfusion imaging within 24 hours of onset will be assessed determine their eligibility for
randomization into the trial. If the patient gives informed consent they will be randomised
using a central computerised allocation process to either standard of care (no intravenous
thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase before undergoing
intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded
endpoint (PROBE) design.
Trial website
https://clinicaltrials.gov/show/NCT04454788
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Andrew Bivard, PHD
Address 0 0
Country 0 0
Phone 0 0
+6193424424
Fax 0 0
Email 0 0
abivard@unimelb.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04454788